Heritability of Cognitive Functions in Families of Successful Cognitive Aging Probands from the Central Valley of Costa Rica

Article type: Research Article

Authors: Greenwood, Tiffany A.^a | Beeri, Michal S.^{b; c; d} | Schmeidler, James^b | Valerio, Daniel^{e; f} | Raventós, Henriette^{f; g} | Mora-Villalobos, Lara^f | Camacho, Karla^f | Carrión-Baralt, José R.^h | Angelo, Gary^b | Almasy, Lauraⁱ | Sano, Mary^{b; j} | Silverman, Jeremy M.^{b; d; j; *}

Affiliations: [a] Department of Psychiatry, University of California San Diego, La Jolla, CA, USA | [b] Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA | [c] Geriatric Research, Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, New York, NY, USA | [d] Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY, USA | [e] Hospital Nacional de Geriatría de Costa Rica, San José, Costa Rica | [f] Centro de Investigación en Biología Molecular y Celular, Universidad de Costa Rica, San José, Costa Rica | [g] Escuela de Biología, Universidad de Costa Rica, San José, Costa Rica | [h] Gerontology Program, Department of Human Development, Graduate School of Public Health, University of Puerto Rico Medical Sciences Campus, Rio Piedras, Puerto Rico | [i] Southwestern Foundation for Biomedical Research, San Antonio, Texas, USA | [j] Research and Development Service, James J. Peters Veterans Affairs Medical Center, Bronx, New York, NY, USA

Correspondence: [*] Correspondence to: Jeremy M. Silverman, Ph.D., Department of Psychiatry, Box 1230, Mount Sinai School of Medicine, One Gustave L. Levy Place, NY 10029, USA. Tel.: +212 659 8822; Fax: +212 659 5626; E-mail: [email protected].

Abstract: We sought to identify cognitive phenotypes for family/genetic studies of successful cognitive aging (SCA; maintaining intact cognitive functioning while living to late old age). We administered a battery of neuropsychological tests to nondemented nonagenarians (n = 65; mean age = 93.4 ± 3.0) and their offspring (n = 188; mean age = 66.4 ± 5.0) from the Central Valley of Costa Rica. After covarying for age, gender, and years of education, as necessary, heritability was calculated for cognitive functions at three pre-defined levels of complexity: specific neuropsychological functions (e.g., delayed recall, sequencing), three higher level cognitive domains (memory, executive functions, attention), and an overall neuropsychological summary. The highest heritability was for delayed recall (h2 = 0.74, se = 0.14, p < 0.0001) but significant heritabilities involving memory were also observed for immediate recall (h2 = 0.50), memory as a cognitive domain (h2 = 0.53), and the overall neuropsychological summary (h2 = 0.42). Heritabilities for sequencing (h2 = 0.42), fluency (h2 = 0.39), abstraction (h2 = 0.36), and the executive functions cognitive domain (h2 = 0.35) were also significant. In contrast, the attention domain and memory recognition were not significantly heritable in these families. Among the heritable specific cognitive functions, a strong pleiotropic effect (i.e., evidence that these may be influenced by the same gene or set of genes) for delayed and immediate recall was identified (bivariate statistic = 0.934, p < 0.0001) and more modest but significant effects were found for four additional bivariate relationships. The results support the heritability of good cognitive function in old age and the utilization of several levels of phenotypes, and they suggest that several measures involving memory may be especially useful for family/genetic studies of SCA.

Keywords: Family studies, hispanic population, neuropsychological phenotype, oldest-old, successful cognitive aging

DOI: 10.3233/JAD-2011-110782

Journal: Journal of Alzheimer's Disease, vol. 27, no. 4, pp. 897-907, 2011